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Adoptive cell transfers (ACTs) can interact specifically with inflamed tissues, but lack a mechanism for transport through viscous biological barriers such as mucus when administered locally. Further, maintaining cell function is challenging due to the loss of cellular phenotypes in diseased microenvironments. In this work, the use of magnetically controlled helical microrobots is examined to transport macrophages through physiologically representative mucus and maintain functional phenotypes through drug elution for improved cell delivery. Two-photon lithography and sputter coating are used to fabricate helical particles that are embedded with a small molecule drug, dexamethasone, and coated with nickel and titanium. The attachment of macrophages to the helices and the analysis of how the cells influence the trajectories of cell-helix complexes when exposed to a rotating magnetic field are investigated. Additionally, the transport of complexes is compared in aqueous solutions and artificial mucus, noting a nonzero cell-helix complex velocity in the most viscous mucus for potential therapeutic implications. It is found that attached macrophages display no loss of viability after actuation and exhibit directed polarization toward a prescribed anti-inflammatory phenotype due to the sustained release of dexamethasone from the microrobots. This system provides a proof-of-concept for using magnetically controlled ACTs to enhance the treatment of inflammatory diseases.
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http://dx.doi.org/10.1002/smll.202505946 | DOI Listing |
Biotechnol J
September 2025
Department of Biochemical Engineering, University College London, London, UK.
Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively.
View Article and Find Full Text PDFEur J Immunol
September 2025
Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Memory T cells, a sizable compartment of the mature immune system, enable enhanced responses upon re-infection with the same pathogen. We have recently shown that virus-experienced innate acting T (T) cells can modulate infectious or autoimmune diseases through TCR-independent IFN-γ production. However, how these cells arise remains unclear.
View Article and Find Full Text PDFAdv Pharm Bull
July 2025
Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Shillong, India 793022.
One of the major reason of deaths due to cancer globally is caused by lung cancer of which the two main types include non-small cell and small cell lung cancer. The onset of treatment-resistance in cancer cells offers a serious obstacle to the therapeutic effect despite that primary conventional treatments have provided significant benefits and cures. Cancer immunotherapy offers a compelling alternative in patients by utilizing their immune system to enhance its ability to fight against tumors.
View Article and Find Full Text PDFNat Rev Immunol
September 2025
La Jolla Institute for Immunology, La Jolla, CA, USA.
Immunometabolism, the intersection of cellular metabolism and immune function, has revolutionized our understanding of T cell biology. Changes in cellular metabolism help guide the development of thymocytes and the transition of T cells from naive to effector, memory and tissue-resident states. Innate-like T cells are a unique group of T cells with special characteristics.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
Background: Patients with acute myeloid leukemia (AML) are often older, which brings challenges of endurance and persistent efficacy of autologous chimeric antigen receptor (CAR)-T cell therapies. Allogenic CAR-natural killer (NK) cell therapies may offer reduced toxicities and enhanced anti-leukemic potential against AML. CD33 CAR-NK cells have been investigated for AML therapy.
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